title: Diltiazem and/or desferrioxamine administered at the time of reperfusion fail to improve post-ischemic recovery in the isolated rat heart after long-term hypothermic storage.
abstract: The ability of diltiazem and/or desferrioxamine to enhance the recovery of cardiac contractile function during reperfusion after prolonged hypothermic storage was assessed. Isolated rat hearts were arrested with St. Thomas' Hospital Cardioplegic Solution and stored for 10 h at 4 degrees C. Reperfusion in the Langendorff mode was initially carried out with crystalloid perfusate with or without added diltiazem (0.5 mumol/l) and/or desferrioxamine (15, 50, 100, 150 or 250 mumol/l). After 15 min the drugs were discontinued and the hearts were perfused for a further 45 min. Diltiazem reduced leakage of creatine (CK) kinase during the first 15 min of reperfusion from 102 +/- 8 IU/15 min/g dry wt to 67 +/- 9 IU/15 min/g dry wt (P less than 0.05). However, during the subsequent period of diltiazem-free perfusion, CK leakage was similar to control values (131 +/- 24 vs 142 +/- 34 IU/45 min/g dry wt, respectively). After 1 h of reperfusion there was no significant difference in total CK leakage between the diltiazem and the control groups (198 +/- 32 vs 244 +/- 39 IU/60 min/g dry wt, respectively). Desferrioxamine had no effect on CK leakage at any of the doses studied. Diltiazem significantly reduced leakage of enzyme during the initial reperfusion phase when combined with desferrioxamine; however, as with diltiazem alone, this protection was lost after the drug was withdrawn. Post-ischemic contents of adenosine triphosphate and creatine phosphate were similar in all groups as was the final recovery of function, as assessed by left ventricular developed pressure at an end-diastolic pressure of 5 mmHg. In conclusion, neither diltiazem nor desferrioxamine nor both together could be shown to confer benefit during reperfusion after long-term storage.
authors.affiliation: Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Galiñanes
authors.forename: D J
authors.initials: DJ
authors.lastname: Hearse
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D003402:Creatine Kinase / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D004110:Diltiazem; D003676:Deferoxamine